Known biomaterials comprising inorganic materials, which may be implanted to a living body, can bond directly to bones but are defective in being friable and too high in elasticity compared with natural bones (cf. Non-patent Literatures 1 to 4). Known biomaterials comprising only organic materials do not bond directly to bones, are weak in strength and do not produce adhesion to the surrounding tissues, whereby the rebuilding of the tissues such as bones in a living body is delayed in the inductive tissue regeneration method.
In order to solve the above problems, it is proposed, for instance, in JP-A-7-101708 (Patent Literature 1) to provide a biomaterial composite (e.g. a composite of apatite as the inorganic material and collagen as the organic material) in a shaped form having physical properties analogous to bones in a living body, said biomaterial composite being prepared by adding a collagen solution admixed with phosphoric acid gradually to a suspension of calcium hydroxide, collecting the deposited material by filtration and drying the collected material, followed by compression molding.
Since the biomaterial composite as proposed above has a Young's modulus to the same extent as soft bones, it is further proposed in JP-A-11-199209 (Patent Literature 2) to provide an improved biomaterial composite of collagen and a calcium phosphate compound having a Young's modulus to the same extent as hard bones, said improved biomaterial composite being prepared by dropwise addition of an aqueous phosphoric acid solution containing collagen and an aqueous solution containing a calcium salt simultaneously to a reaction vessel and compression molding of the deposited material.
This collagen/calcium phosphate composite has physical properties similar to bones in a living body and is a biomaterial having excellent characteristics in bone substitution, tissue reconstruction, strength, etc. However, it has a problem in becoming friable with the lapse of time after implantation in a living body to degrade finally. To solve this problem, it is proposed in JP-A-2001-276207 (Patent Literature 3) to use a cross-linking agent in either on or after the compression step in the preparation of a collagen/calcium phosphate composite so as to make such composite cross-linked whereby the resistance to degradation on the implantation in a living body is enhanced while keeping a sufficient strength.
On the other hand, M. Neo et al. have studied and reported on the reaction between bioactive ceramics (indicating inorganic materials capable of binding to bones directly) and bones. According to such report, the implantation of a crystallized glass A-W in a rat tibia for 2 weeks resulted in formation of a hydroxyapatite layer on the surface of said glass by its reaction with body fluid. Thus, bones (cells) do not recognize the glass-hydroxyapatite composite as a xenobiotic (cf. Non-patent Literature 4).    Patent Literature 1: JP-A-7-101708;    Patent Literature 2: JP-A-11-199209;    Patent Literature 3: JP-A-2001-276207;    Patent Literature 4: JP-A-2003-321500;    Non-patent Literature 1: L. L. Hench and J. Wilson, “An Introduction to Bioceramics”, World Scientific Publishing Co. Pte. Ltd, Singapore, 1993, pp. 1-24;    Non-patent Literature 2: L. L. Hench, R. J. Splinter, W. C. Allen and T. K. Greenlee, Journal of Biomedical Materials Research, 1971, Vol. 2, p. 117-141, “Bonding Mechanism at The Interface of Ceramics Prosthetic Materials”;    Non-patent Literature 3: M. Jarcho, J. L. Kay, R. H. Gumaer and H. P. Drobeck, Journal of Bioenergetics, 1977, Vol. 1, p. 79-92, “Tissue, Cellular and Subcellular Events at Bone-ceramic Hydroxyapatite Interface”;    Non-patent Literature 4: M. Neo, T. Nakamura, C. Ohtsuki, T. Kokubo and T. Yamamoto, Journal of Biomedical Materials Research, 1993, Vol. 27, p. 999-1006.